Inflammation-related genes are associated with epigenetic aging in HIV.

TitleInflammation-related genes are associated with epigenetic aging in HIV.
Publication TypeJournal Article
Year of Publication2019
AuthorsSundermann, EE, Hussain, M, Moore, D, Horvath, S, Lin, DTS, Kobor, MS, Levine, AJ
Corporate AuthorsHNRP Group
JournalJ Neurovirol
Volume25
Issue6
Pagination853-865
Date Published2019 12
ISSN1538-2443
KeywordsCHARTER, Internal
Abstract

Chronic inflammation is characteristic of both HIV and aging ("inflammaging") and may contribute to the accelerated aging observed in people living with HIV (PLWH). We examined whether three inflammation-related single-nucleotide polymorphisms (SNPs) were risk factors for accelerated aging and HIV-associated, non-AIDS (HANA) conditions among PLWH. We examined 155 postmortem cases with HIV (mean age = 47.3, 81% male, 68% self-reported White) from the National NeuroAIDS Tissue Consortium who had pre-mortem neurobehavioral/medical/virologic data and epigenomic data from occipital cortex tissue. Accelerated aging was measured according to the Epigenetic Clock; an aging biomarker based on DNA methylation levels. Past or current age-associated HANA conditions including cerebrovascular, liver and kidney disease, chronic obstructive pulmonary disease, cancer, and diabetes were determined via self-report. Epigenetic Aging Z-scores and likelihood of past/current HANA conditions were compared between major allele homozygotes and minor allele carriers for each SNP (IL-6 - 174G>C, IL-10 - 592C>A, TNF-α - 308 G>A) separately. Analyses were adjusted for relevant demographic/clinical factors. Epigenetic aging (e.g., higher Z-scores) was significantly greater in IL-6 C allele carriers (p = .002) and IL-10 CC homozygotes (p = .02) compared to other genotype groups. The likelihood of any past/current HANA condition did not differ by IL-10 genotype but was 3.36 times greater in IL-6 C allele carriers versus others (OR = 3.36, 95%CI = 1.09-10.34, p = .03). TNF-α genotype was not associated with epigenetic aging or HANA conditions. IL-6 and IL-10 SNPs may help to identify PLWH who are at high risk for accelerated aging. These insights into pathophysiological pathways may inform interventional approaches to treat rapid aging among PLWH.

DOI10.1007/s13365-019-00777-4
Alternate JournalJ. Neurovirol.
PubMed ID31286441
PubMed Central IDPMC6923602
Grant ListR25 MH108389 / MH / NIMH NIH HHS / United States
HHSN271201000030C / MH / NIMH NIH HHS / United States
R01 DA030913 / DA / NIDA NIH HHS / United States
R01 MH096648 / MH / NIMH NIH HHS / United States
P30 MH062512 / MH / NIMH NIH HHS / United States
N01 MH022005 / MH / NIMH NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R25 MH081482 / MH / NIMH NIH HHS / United States
HHSN271201000036C / MH / NIMH NIH HHS / United States
T32 DA031098 / DA / NIDA NIH HHS / United States